MORPHINE
ALLOWS FOR DOSE-RELATED ANALGESIA AND **INCREASED PAIN TOLERANCE
CAN CAUSE EUPHORIA; HOWEVER, IF ADMINISTERED TO A PERSON WHO IS PAIN FREE, IT CAN CAUSE DYSPHORIA, ANXIETY, MENTAL CLOUDING
SIDE EFFECTS - RESPIRATORY DEPRESSANT, COUGH SUPPRESSANT
MORPHINE BIPHASIC DOSE-DEPENDENT EFFECT ON BODY TEMPERATURE
LOW DOSE - CAUSES A DECREASE IN BODY TEMPERATURE
HIGH DOSE - CAUSES AN INCREASE IN BODY TEMPERATURE
HYDROMORPHONE
(DILAUDID)
ORAL ADMINISTRATION (15-30 MIN)
IV ADMINISTRATION (5 MIN)
RAPIDLY ABSORBED, HIGH 1ST PASS METABOLISM
**3-5X MORE POTENT WHEN GIVEN ORALLY AS MORPHINE (NO INACTIVE/ACTIVE METABOLITES - NO NEED TO WORRY ABOUT PATIENT TO PATIENT VARIABILITIES)
USED FOR MILD TO STRONG PAIN IN HOSPITALS
PHARMACOKINETICS SIMILAR TO MORPHINE
FENTANYL
MANY DIFFERENT WAYS OF ADMINISTERING
ORAL, BUCCAL (5-15 min.), IM (7-8 min.), NASAL SPRAY, IV (immediate), TRANSDERMAL (6h), LOLLIPOPS, LOZENGES
HIGHLY LIPOPHILIC - GETS THROUGH MEMBRANES QUICKLY
80x ANALGESIC POTENCY OF MORPHINE, 10x ANALGESIC POTENCY OF HYDROMORPHONE
**USED FOR BREAKTHROUGH PAIN IN COMBINATION W/ ANOTHER OPIOID FOR CHRONIC PAIN
**HIGH ABUSE POTENTIAL
**SHORT TERM RELIEF
INTERMEDIATE OPIOIDS
**OXYCODONE - SIMILAR EFFICACY TO MORPHINE BUT HAS BETTER ORAL BIOAVAILABILITY (THEBAINE DERIVATIVE)
METHADONE - HIGH POTENCY, LONG DURATION OF ACTION, GOOD ORAL BIOAVAILABILITY, A LOT OF INTER-PATIENT VARIABILITY
**USED FOR OPIOID ADDICTION
BUPRENORPHINE - SL/TD ADMINISTRATION, MU OPIOID EFFICACY AGONIST AND HAS KAPPA ANTAGONIST ABILITIES (GOOD FOR ANALGESIA AND OPIOID ADDICTIONS)
WEAK OPIOIDS
TRAMADOL - WEAK MU AGONIST W/ 5-HT AND NOREPINEPHRINE REUPTAKE INHIBITION (GOOD ORAL BIOAVAILABILITY)
**COMBINES ANTIDEPRESSANT REACTIONS W/ OPIOID REACTIONS
TAPENTADOL - MU AGONIST W/ NE REUPTAKE INHIBITION (B/C NO SEROTONIN REUPTAKE INHIBITION AND STRONG NE REUPTAKE INHIBITION W/ SAME MECHANISM AS COCAINE AND AMPHETAMINE => **HIGH POTENTIAL FOR ABUSE)
CODEINE METABOLISM
CATALYZED TO MORPHINE BY CYP2D6 ENZYME
POLYMORPHISMS IN CYP2D6 =>
1.) INABILITY TO CONVERT CODEINE TO MORPHINE IN 10% OF CAUCASIANS
2.) ULTRA-RAPID CATALYSIS OF CODEINE TO MORPHINE AND AN INCREASE IN SENSITIVITY IN 4-5% OF US POPULATION AND 16-28% OF NORTH AFRICANS, ETHIOPIANS, AND ARABS
NALOXONE (NARCANE)
OPIATE ANTAGONIST - REVERSES RESPIRATORY EFFECTS OF OPIOID AGONISTS
PHARMACOKINETICS =
IM, SUBQ = 2-5 MIN., INHALATION ~5 MIN., INTRANASAL 8-13 MIN., IV ~2 MIN.
DURATION OF ACTION = 30-120 MIN. (REPEATED DOSES ARE USUALLY NEEDED)
REVERSES ALL EFFECTS OF OPIOID AGONISTS AND BLOCKS MU, KAPPA, AND DELTA RECEPTORS
ARACHIDONIC ACID
EICOSANOID PRECURSOR - RELEASED FROM PHOSPHOLIPID MEMBRANE => EICOSANOID SYNTHESIS
OXYGENATED BY CYCLOOXYGENASE, LIPOOXYGENASE, OR CYTOCHROME P450 TO => EICOSANOID PRODUCT
MOST IMPORTANT PRODUCT = PROSTANOIDS - MAINTAIN KEY ROLES IN PAIN SENSING
PROSTANOIDS
PRODUCED BY OXYGENATION BY 2 ENZYMES - COX-1 AND COX-2
1.) POSTAGLANDIN
2.) PROSTACYCLIN
3.) THROMBOXANE (KEY ROLE IN BLOOD CLOTTING)
ALL ARE LOCALLY PRODUCED FOR IMMEDIATE ACTION
COX-1
CONTINUOUSLY MADE AND AVAILABLE TO THE BODY 24/7
PROMOTES CLOTTING, PROTECTS GI MUCOSA, MAINTAINS KINDEY VASODILATION
I.E. ALL REGULAR PHYSIOLOGICAL FUNCTIONS
COX-2
INDUCIBLE BY VARIOUS INSULTS AND PRODUCTS INVOLVED IN INFLAMMATION/CANCER
COX-2 INHIBITORS CAN BE TAKEN FOR ARTHRITIS
ACTIVATED BY LOCAL INFLAMMATION, MODULATE PAIN, PERCEPTION AND PROMOTES FEVER
NSAIDS / ASPIRIN
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
BLOCK ENZYMES (SELECTIVELY, NON-SELECTIVELY, REVERSIBLY, IRREVERSIBLY)
INVOLVED IN SYNTHESIS OF PROSTAGLANDIN-2 CYCLOOXYGENASE AND PROSTANOID
MECHANISM OF ACTION OF NSAIDS/ASPIRIN
DECREASED VASODILATION BY PRG-2 WHICH MEANS LESS VASODILATION AND LESS EDEMA
LESS SENSITIZATION OF NOCICEPTIVE NERVE ENDINGS TO BK/5-HT MEDIATORS (IF NO PRG-2 PRODUCED THEN CAN’T RESPOND TO BK/5-HT STIMULUS)
ANTIPYRETIC - DUE TO DECREASE IN PRG-2 RESPONSE TO IL-1
ANTIPLATELET - (IR)REVERSIBLE (ASPIRIN) INHIBITION OF THROMBOXANE SYNTHESIS ; HOWEVER’ WHERE OTHER TISSUES CAN JUST MAKE MORE THROMBOXANE, PLATELETS AREN’T CELLS AND TAKE A LONG TIME TO MAKE MORE THROMBOXANE
ADVERSE EFFECTS OF COX-1 INHIBITION
GASTRIC ULCERS
BLEEDING
ACUTE RENAL FAILURE
DUE TO FAILURE TO MAKE PRG
ADVERSE EFFECTS OF COX-2 INHIBITION
REDUCES INFLAMMATION
REDUCES PAIN
REDUCES FEVER
INHIBITION OF COX => DECREASED ABILITY OF BLOOD TO CLOT (MI RISK)
NSAID SELECTIVITY FOR COX-1/2
VARIED SELECTIVITY
WIDE RANGE OF DURATION 1-60HRS
MANY ARE SELECTIVELY IN THE MIDDLE
PHARMACOKINETICS OF ASPIRIN
ABSORPTION - STOMACH/INTESTINES
DISTRIBUTION - READILY, INTO MOST FLUIDS/TISSUES
METABOLISM - HEPATIC
CONTRAINDICATED USES - FEVERISH CHILDREN (CAUSES REYE’S SYNDROME OF LIVER DEGENERATION AND ENCEPHALITIS IF TREATED W/ ASPIRIN DURING A VIRAL INFECTION RELATED TO VARICELLA/INFLUENZA)
**FATAL OVERDOSE IS COMMON IN CHILDREN
ACETOMINOPHEN (APAP)
ANALGESIC AND ANTIPYRETIC
NOT AN NSAID BUT HAS SIMILAR EFFECTS
INHIBITS PRG-2 SYNTHESIS VIA CNS INHIBITION OF COX (NOT PERIPHERAL)
DOES NOT PROMOTE ULCERS, BLEEDING, OR RENAL FAILURE
PERIPHERALLY BLOCKS GENERATION OF PAIN IMPULSES AND INHIBITS HYPOTHALAMIC HEAT REGULATION
LIVER METABOLISM
LIVER METABOLISM OF APAP
MAJOR PATHWAY - PRODUCES A NON TOXIC METABOLITE
MINOR PATHWAY - PRODUCES A HIGHLY REACTIVE INTERMEDIATE AT TOXIC APAP LEVELS
CAN NOT KEEP UP WITH METABOLISM OF APAP AND INCREASES CONCENTRATION OF REACTIVE INTERMEDIATE => HEPATIC TOXICITY AND NECROSIS
ALCOHOL CONSUMPTION CAN ALSO CAUSE THIS
PHARMACOKINETICS OF APAP - ACETYLCYSTEINE FOR OVERDOSE
POTENTIAL TOXICITIES OF NSAIDS DUE TO PROSTANOID INHIBITION
- ) GASTRIC MUCOSAL DAMAGE, ULCERS, BLEEDING OBSTRUCTION - DUE TO PGE INHIBITION
- ) BLEEDING - INHIBITION OF PLATELET AGGREGATION
- ) LIMITATION OF RENAL BLOOD FLOW - NA+ AND WATER RETENTION, ACUTE, RENAL FAILURE, HYPERKALEMIA, HYPERTENSION
- ) DELAY/PROLONGATION OF LABOR
- ) ASTHMA AND ANAPHYLACTOID REACTIONS
